We will attempt to establish the etiology and pathogenesis of multiple sclerosis (MS) using several inter-dependent approaches. We will attempt to recover virus from MS patients in various stages of the disease, search for morphologic evidence of the presence of virus, and utilize immunologic methods to look for evidence of continued infection of MS patients. We will study the effects on brain cells in vivo and in vitro of an agent previously recovered by us from MS brain and any other agents which may be considered to be involved in the etiology of MS. We will look for sero-epidemiologic differences between populations exhibiting high and low risks for developing MS. We will characterize in a serial prosepctive fashion, parameters of humoral and cell-mediated altered immune responsiveness, in correlation with the clinical course of a closely studied group of MS patients. These investigations may yield a more specific laboratory diagnostic test for multiple sclerosis. We will study biosynthetic process during remyelinaton, as compared with initial myelination in vitro. We will attempt to enhance remyelination in vitro with agents found to have a favorable effect on initial myelination. Techniques will include the methods of virology, molecular biology, immunology, CNS organ culture, low and high voltage transmission and scanning electron microscopy, autoradiography and neurochemistry in conjunction with detailed neurologic characterization of patients participating in studies.